PHYLOGENOMIC, TRANSCRIPTOMIC, VIROMIC, AND IMMUNOPROTEOMIC DETERMINANTS OF NECROTIZING ENTEROCOLITIS

坏死性小肠结肠炎的系统基因组、转录组、病毒组和免疫蛋白质组决定因素

基本信息

  • 批准号:
    10164835
  • 负责人:
  • 金额:
    $ 58.45万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2017
  • 资助国家:
    美国
  • 起止时间:
    2017-09-06 至 2023-05-31
  • 项目状态:
    已结题

项目摘要

Project Summary Necrotizing enterocolitis in very low birth weight infants remains a major challenge. Our reactive clinical approach to necrotizing enterocolitis has changed little in four decades. Morbidity and mortality from necrotizing enterocolitis remain unacceptably high, and preventive strategies rely on interventions with limited, if any, efficacy. We have assembled an extensive set of specimens, accompanied by rich clinical metadata, with which to define mechanisms that underlie the development of necrotizing enterocolitis in very preterm infants. Our proposal extends our recently published findings that a gut bacterial dysbiosis, characterized by over-representation of Gammaproteobacteria and under-representation of obligate anaerobic bacteria, precede, and plausibly contribute to, the development of necrotizing enterocolitis. Our overarching hypothesis is that identifiable microbial and/or host mechanisms signify an infant at risk for necrotizing enterocolitis. Our long-term goals are to use our knowledge of microbial-driven pathophysiology in necrotizing enterocolitis to build interventions to prevent the assembly of dysbiotic gut bacterial populations, to characterize the host biology prior to the sudden appearance of necrotizing enterocolitis. By generating these data, we hope to lessen the severity of necrotizing enterocolitis, or to prevent it altogether. Our Specific Aims are: (1) Conduct a comprehensive genomic analysis of gut bacteria prior to necrotizing enterocolitis onset, and (2) Define the gut biology and host response prior to necrotizing enterocolitis onset. All specimens from cases will be those obtained before this event occurred. Control materials will be matched to cases, according to gestational age at birth, and day of life specimens were produced. To accomplish these Aims, we will use our archive of pre-event stools and sera/plasmas from 977 very low birthweight infants from three neonatal intensive care units. Forty-six of these infants experienced NEC, after excluding those who also had congenital heart disease. We will employ genomic characterization of isolates, transcriptomics, metabolomics, viromics, and immunoproteomics in coordinated analyses to illuminate microbial and host biology underlying necrotizing enterocolitis. We will also interrogate populations of bacteria associated with protection from necrotizing enterocolitis. All studies will initially analyze a primary cohort from St. Louis, and then validate findings in specimens from Oklahoma City and Louisville. These case-control and time-series comparisons will provide mechanistic insight into an intractable and highly consequential complication of preterm birth, using an exceptionally relevant system, i.e., the colonized human infant. By project conclusion, we will generate mechanistically-informed data to guide attempts to better anticipate, treat, or, ideally, prevent, necrotizing enterocolitis, a devastating complication of preterm birth.
项目摘要 极低出生体重儿的坏死性小肠结肠炎仍然是一个重大挑战。我们的反应性临床 坏死性小肠结肠炎的治疗方法四十年来几乎没有改变。的患病率和死亡率 坏死性小肠结肠炎仍然高得令人无法接受,预防策略依赖于有限的干预, 如果有的话,有效性。我们已经收集了大量的标本,伴随着丰富的临床元数据, 以确定极早产儿坏死性小肠结肠炎发生的机制, 婴儿。我们的建议扩展了我们最近发表的发现,即肠道细菌生态失调,其特征是 γ-变形菌的代表性过高,而专性厌氧菌的代表性不足, 在坏死性小肠结肠炎的发展之前,并且可能有助于坏死性小肠结肠炎的发展。 我们的总体假设是,可识别的微生物和/或宿主机制表明婴儿在 坏死性小肠结肠炎的风险。我们的长期目标是利用我们对微生物驱动的知识 坏死性小肠结肠炎的病理生理学,以建立干预措施,防止肠道菌群失调 细菌种群,以表征宿主生物学之前,突然出现坏死 肠炎通过生成这些数据,我们希望减轻坏死性小肠结肠炎的严重程度,或预防 它完全。 我们的具体目标是:(1)在接种前对肠道细菌进行全面的基因组分析。 坏死性小肠结肠炎发作,和(2)定义坏死性小肠结肠炎前的肠道生物学和宿主反应 小肠结肠炎发作。病例的所有标本均为该事件发生前获得的标本。控制 材料将匹配的情况下,根据出生时的胎龄,和一天的生活标本, 制作。 为了实现这些目标,我们将使用我们的977例非常严重的事件前粪便和血清/血浆档案, 三个新生儿重症监护室的低出生体重儿。这些婴儿中有46人经历了NEC, 在排除了那些同时患有先天性心脏病的人之后。我们将采用基因组表征, 分离株,转录组学,代谢组学,病毒组学和免疫蛋白质组学的协调分析,以阐明 微生物和宿主生物学基础坏死性小肠结肠炎。我们还将研究 与保护免受坏死性小肠结肠炎有关。所有研究最初将分析来自以下人群的主要队列: 圣路易斯,然后验证来自俄克拉荷马州市和路易斯维尔的标本中的发现。这些病例对照和 时间序列比较将提供一个棘手的和高度后果的机械洞察力 早产并发症,使用特别相关的系统,即,被殖民的人类婴儿 在项目结束时,我们将生成机械信息数据,以指导尝试更好地 预测、治疗或理想情况下预防坏死性小肠结肠炎,这是早产的毁灭性并发症。

项目成果

期刊论文数量(26)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Approaches for characterizing and tracking hospital-associated multidrug-resistant bacteria.
Cotrimoxazole Prophylaxis Increases Resistance Gene Prevalence and α-Diversity but Decreases β-Diversity in the Gut Microbiome of Human Immunodeficiency Virus-Exposed, Uninfected Infants.
The effect of legume supplementation on the gut microbiota in rural Malawian infants aged 6 to 12 months.
  • DOI:
    10.1093/ajcn/nqaa011
  • 发表时间:
    2020-02
  • 期刊:
  • 影响因子:
    0
  • 作者:
    M. I. Ordiz;Stefan Janssen;G. Humphrey;G. Ackermann;Kevin B. Stephenson;Sophia E. Agapova;O. Divala;Yankho Kaimila;K. Maleta;Caroline Zhong;R. Knight;Indi Trehan;P. Tarr;B. Rusconi;M. Manary
  • 通讯作者:
    M. I. Ordiz;Stefan Janssen;G. Humphrey;G. Ackermann;Kevin B. Stephenson;Sophia E. Agapova;O. Divala;Yankho Kaimila;K. Maleta;Caroline Zhong;R. Knight;Indi Trehan;P. Tarr;B. Rusconi;M. Manary
Effect of amoxicillin on the gut microbiome of children with severe acute malnutrition in Madarounfa, Niger: a retrospective metagenomic analysis of a placebo-controlled trial.
  • DOI:
    10.1016/s2666-5247(23)00213-6
  • 发表时间:
    2023-11
  • 期刊:
  • 影响因子:
    38.2
  • 作者:
    Schwartz, Drew J.;Langdon, Amy;Sun, Xiaoqing;Langendorf, Celine;Berthe, Fatou;Grais, Rebecca F.;Trehan, Indi;Isanaka, Sheila;Dantas, Gautam
  • 通讯作者:
    Dantas, Gautam
Draft Genome Sequence of a Mycobacterium Strain Isolated from a Clinical Wound Sample.
{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Gautam Dantas其他文献

Gautam Dantas的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Gautam Dantas', 18)}}的其他基金

Impact of early-life perturbations on pediatric microbiome maturation
早期生活扰动对儿科微生物组成熟的影响
  • 批准号:
    10424578
  • 财政年份:
    2021
  • 资助金额:
    $ 58.45万
  • 项目类别:
Impact of early-life perturbations on pediatric microbiome maturation
早期生活扰动对儿科微生物组成熟的影响
  • 批准号:
    10298201
  • 财政年份:
    2021
  • 资助金额:
    $ 58.45万
  • 项目类别:
Impact of early-life perturbations on pediatric microbiome maturation
早期生活扰动对儿科微生物组成熟的影响
  • 批准号:
    10634654
  • 财政年份:
    2021
  • 资助金额:
    $ 58.45万
  • 项目类别:
Occupational Exposure and Health Risk from Dairy Microbiome and Resistome to Dairy Farm Workers
乳制品微生物组和 Resistome 对奶牛场工人的职业暴露和健康风险
  • 批准号:
    10165408
  • 财政年份:
    2018
  • 资助金额:
    $ 58.45万
  • 项目类别:
Tunable therapeutic modulation of the gut microbiome by engineered probiotics
通过工程益生菌对肠道微生物组进行可调节的治疗调节
  • 批准号:
    10451749
  • 财政年份:
    2018
  • 资助金额:
    $ 58.45万
  • 项目类别:
Tunable therapeutic modulation of the gut microbiome by engineered probiotics
通过工程益生菌对肠道微生物组进行可调节的治疗调节
  • 批准号:
    9977923
  • 财政年份:
    2018
  • 资助金额:
    $ 58.45万
  • 项目类别:
Tunable therapeutic modulation of the gut microbiome by engineered probiotics
通过工程益生菌对肠道微生物组进行可调节的治疗调节
  • 批准号:
    9761466
  • 财政年份:
    2018
  • 资助金额:
    $ 58.45万
  • 项目类别:
Tunable therapeutic modulation of the gut microbiome by engineered probiotics
通过工程益生菌对肠道微生物组进行可调节的治疗调节
  • 批准号:
    10207474
  • 财政年份:
    2018
  • 资助金额:
    $ 58.45万
  • 项目类别:
PHYLOGENOMIC, TRANSCRIPTOMIC, VIROMIC, AND IMMUNOPROTEOMIC DETERMINANTS OF NECROTIZING ENTEROCOLITIS
坏死性小肠结肠炎的系统基因组、转录组、病毒组和免疫蛋白质组决定因素
  • 批准号:
    9559708
  • 财政年份:
    2017
  • 资助金额:
    $ 58.45万
  • 项目类别:
PHYLOGENOMIC, TRANSCRIPTOMIC, VIROMIC, AND IMMUNOPROTEOMIC DETERMINANTS OF NECROTIZING ENTEROCOLITIS
坏死性小肠结肠炎的系统基因组、转录组、病毒组和免疫蛋白质组决定因素
  • 批准号:
    9369551
  • 财政年份:
    2017
  • 资助金额:
    $ 58.45万
  • 项目类别:

相似海外基金

AMFaces: Advanced Additive Manufacturing of User-Focused Facial Prostheses with Real-Life Colour Appearance
AMFaces:以用户为中心的面部假体的先进增材制造,具有真实的色彩外观
  • 批准号:
    EP/W033968/1
  • 财政年份:
    2023
  • 资助金额:
    $ 58.45万
  • 项目类别:
    Research Grant
Understanding the appearance mechanism of ferroelectric liquid crystals showing spontaneous polarization in the director and developing their applications.
了解铁电液晶在指向矢中表现出自发极化的出现机制并开发其应用。
  • 批准号:
    23H00303
  • 财政年份:
    2023
  • 资助金额:
    $ 58.45万
  • 项目类别:
    Grant-in-Aid for Scientific Research (A)
Elucidating the mechanism in the color appearance of small-field stimulus on chromatic surroundings
阐明彩色环境中小场刺激的颜色外观机制
  • 批准号:
    22K20317
  • 财政年份:
    2022
  • 资助金额:
    $ 58.45万
  • 项目类别:
    Grant-in-Aid for Research Activity Start-up
Body, appearance, and health surveillance in female youth friendship contexts
女性青少年友谊背景下的身体、外表和健康监测
  • 批准号:
    2690554
  • 财政年份:
    2022
  • 资助金额:
    $ 58.45万
  • 项目类别:
    Studentship
Learning to Recognize Faces Despite Within-Person Variability in Appearance: A Developmental Approach
尽管人与人之间的外表存在差异,但仍要学习识别面孔:一种发展方法
  • 批准号:
    RGPIN-2022-04386
  • 财政年份:
    2022
  • 资助金额:
    $ 58.45万
  • 项目类别:
    Discovery Grants Program - Individual
Path-space Exploration for Light Transport and Appearance Modelling
光传输和外观建模的路径空间探索
  • 批准号:
    RGPIN-2018-05669
  • 财政年份:
    2022
  • 资助金额:
    $ 58.45万
  • 项目类别:
    Discovery Grants Program - Individual
Appearance of negative influences of global warming on crop production and measures against it
全球变暖对农作物生产的负面影响的显现及应对措施
  • 批准号:
    21H02330
  • 财政年份:
    2021
  • 资助金额:
    $ 58.45万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
A sociological study on appearance discrimination during employment selection
就业选择中外表歧视的社会学研究
  • 批准号:
    21K13447
  • 财政年份:
    2021
  • 资助金额:
    $ 58.45万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
The influence of river environment on urban appearance of wildlife
河流环境对野生动物城市面貌的影响
  • 批准号:
    21K12322
  • 财政年份:
    2021
  • 资助金额:
    $ 58.45万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Method for assessing women's perceptions of their appearance in the context of breast cancer care
评估乳腺癌护理背景下女性对其外表的看法的方法
  • 批准号:
    10196213
  • 财政年份:
    2021
  • 资助金额:
    $ 58.45万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了